CTLA-4: A negative regulator of autoimmune disease

Nitin J. Karandikar, Carol L. Vanderlugt, Theresa L. Walunas, Stephen D. Miller*, Jeffrey A. Bluestone

*Corresponding author for this work

Research output: Contribution to journalArticle

331 Scopus citations

Abstract

CTLA-4, a CD28 homologue expressed on activated cells, binds with high affinity to the CD28 ligand, B and-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-161-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vitro administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA- 4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalJournal of Experimental Medicine
Volume184
Issue number2
DOIs
StatePublished - Aug 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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